Somatic Mutation of RET Proto-Oncogene in Sporadic Medullary Thyroid Carcinoma

Abstract

Medullary thyroid carcinoma (MTC) occurs as a sporadic form or as an autosomal dominant inherited familial disorder. Germ-line mutations of the RET proto-oncogene are known to be a cause of familial forms. Even in apparently sporadic cases, however, somatic mutations of RET are detected in 23% to 69% of cases. The most common somatic mutation observed in sporadic MTC is an amino acid substitution (from methionine to threonine) at codon 918. A few other mutations have been reported sporadically. Here we report a case of sporadic MTC whose tumor showed somatic mutation of RET at codon 634 (from cysteine to arginine). A 60-year-old woman was admitted for examination of a neck mass. Her calcitonin level was extremely high and ultrasonography and neck computerized tomography showed a 2-cm mass with heterogeneous internal density. Genetic analysis of her DNA from peripheral blood showed no mutation of the RET gene. The patient underwent successful total thyroidectomy. Pathologic and immunohistochemical study were compatible with MTC. Genetic analysis of the tumor tissue showed the C634R mutation in RET gene. The C634R somatic mutation, one of the most frequent mutations observed in germ-lines in multiple endocrine neoplasia 2A, might have contributed to the tumorgenesis in this sporadic MTC. Cases of MTC with somatic mutations of C634R in the RET gene are rare. Here we report the precise clinical data and clinical course of this rare MTC and we review the reported MTCs with somatic mutations of the RET gene.